BioCryst Pharmaceuticals, Inc. (NASDAQ: BCRX) has announced positive top-line results from its randomized, double-blind, multi-center, placebo-controlled Phase 2 study designed to evaluate the urate-lowering activity and safety of several doses of BCX4208 alone and in combination with selected doses of allopurinol administered once-daily.
The study utilized a factorial design. The primary endpoint was change in serum uric acid concentration (sUA) after 21 days of treatment compared to baseline concentration prior to treatment. Eighty-seven gout patients with sUA concentrations greater than or equal to 8 mg/dL were randomized to receive BCX4208 at daily doses of 20 mg, 40 mg and 80 mg administered orally as monotherapy or in combination with allopurinol at daily doses of 100 mg, 200 mg and 300 mg administered orally.
A dose-response was demonstrated for both BCX4208 and allopurinol, and the combination of BCX4208 and allopurinol was shown to be superior to either drug alone in sUA reduction. The mean reduction in sUA from baseline observed in the nine groups of patients receiving combinations of BCX4208 and allopurinol ranged from 2.4 to 5.6 mg/dL. In five of these nine combination groups, 80 percent or more of the patients achieved a sUA concentration of less than 6 mg/dL. Combinations of lower doses of BCX4208 with allopurinol showed synergistic effects in sUA reduction.
These doses of BCX4208 alone and in combination with allopurinol were generally safe and well-tolerated. Consistent with prior BCX4208 clinical studies, reductions in peripheral blood lymphocytes were observed in patients treated with BCX4208. The protocol included stopping rules for CD4+ cell counts below certain thresholds; no subjects were discontinued for this reason.
“This successful study demonstrates that BCX4208 and allopurinol in combination may synergistically reduce uric acid levels in the blood and supports its continued evaluation as a potential treatment for patients with gout,” said Dr. William P. Sheridan, Chief Medical Officer at BioCryst. “We are now finalizing plans for a 12 week, randomized, controlled study of BCX4208 as add-on therapy in gout patients who have failed to adequately respond to allopurinol. We look forward to starting this study in early 2011 and plan to enroll over 200 patients.”
BCX4208 is a next generation purine nucleoside phosphorylase (PNP) inhibitor with the potential for once-a-day dosing suitable for chronic administration. Previous studies have shown that BCX4208 may have utility in diseases dependent on T-cells, B-cells or uric acid. With its novel mechanism of action, BCX4208 has the potential to address unmet medical needs across a broad spectrum of inflammatory diseases, including gout.
Gout is an inflammatory arthritis that affects up to five million people in the U.S. Gout is caused by higher-than-normal uric acid in the blood, (a condition known as hyperuricemia) that may lead to the buildup of uric acid in synovial fluid around joints and the formation of monosodium urate crystals that result in painful joint inflammation.
Source: BioCryst Pharmaceuticals